Cephalosporin C-type compounds are frequently derived from cephalosporin C which is prepared by fermentation in accordance with the method described in U.S. Pat. No. 3,093,638, and which is now known to have the structure ##SPC1##
Cephalosporin C is a weak antibiotic but is of more importance as a source of 7-aminocephalosporanic acid, commonly abbreviated 7-ACA. The 7-ACA is prepared by known cleavage processes and is used as an intermediate in the process for preparing a variety of cephalosporin antibiotics, e.g., cephalothin, cephaloridine, and cephaloglycin, which are substantially more potent than cephalosporin C.
Since cephalosporin C is quite valuable in these antibiotic preparation processes, those in the art are seeking more efficient methods for extracting the dissolved cephalosporin C from its fermentation liquor, after separation from the fermentation solids, or from the so-called resin eluate solution containing the cephalosporin C. Resin eluate solutions of cephalosporin C are obtained by passing the filtered fermentation liquor through resin columns which absorb or adsorb the cephalosporin C, and then washing the columns with aqueous liquids which dissolve the cephalosporin C therein.
Efficient methods for extracting greater percentages of the cephalosporin C values from fermentation broths and resin eluate solutions are being developed. For example, Harold B. Hayes et al., U.S. Pat. No. 3,641,018, disclose an improved process for the preparation of 7-ACA from cephalosporin C comprising acylating the amino group in the adipamoyl side chain with an .alpha.-halo or .alpha.,.alpha.-dihalo C.sub.2 -C.sub.4 alkanoyl group, before protecting the carboxyl groups, treating with a halogenating agent to convert the amido group in the 7-position to an imino halide, converting the imino halide to an imino ether, and hydrolyzing the imino ether to 7-aminocephalosporanic acid. That improved method is quite significant but it is also one which commits the operator of the process to the production of 7-aminocephalosporanic acid. There is a need in the cephalosporin art for an alternative process for extracting cephalosporin C and other amine group containing cephalosporins from impure or complex solutions containing them which allows one to regenerate the amine group containing cephalosporin compound.
It is an object of this invention to provide an alternative process for extracting valuable amine group containing cephalosporin compounds from solutions thereof as pentavalent phosphorus amidated derivatives thereof which, if desired, can be easily reversed to the parent amino-group containing cephalosporin compounds.
It is another object of this invention to provide an improved alternative process for obtaining cephalosporin nuclei compounds from the fermentation-derived parent substances.